For the manufacturing of tablets and capsules containing oral grade penicillins or cephalosporins it is generally found that the crystalline material has no satisfactory flowability so that controlled dosage during tablet and capsule manufacturing-processes is not guaranteed. Therefore it is customary to produce a granulate first by mixing the crystalline powder (1-30 .mu.m) with a small amount of organic solvent (e.g. alcohol) sometimes diluted with water. It is required then to admix other components as binders (e.g. PVP) and fillers (e.g. lactose) for obtainment of granulates with satisfactory particle size distribution and strength. However, it will not be possible to achieve a high dosage per tablet unless relatively large tablets are made.
The granulation process generally takes place in a high shear mixer granulator by which dense particles of a suitable particle size distribution are produced. After the granulation process the material (particles of approximately 400-500 .mu.m average diameter) is dried. It is found that while using only water as binding liquid (i.e. no alcohol, no binding agents) wherein Pen VK has been solved which liquid leads to binding into granules during the drying process, the batch-wise operated high shear granulators can not give a satisfactory particle size distribution while excessive fouling of the apparatus occurs.
The use of an organic solvent in this process is a clear disadvantage because of the fact that one has to dry the final product extensively due to the required low levels of solvent in the final dosage form. From a process point of view one would have remarkably less environmental problems if the organic solvent could be circumvented.
Furthermore, the absence of binders could give granulates which can be used in high potency tablets or capsules.
We have found now two granulation methods wherein the organic solvent is not needed for obtaining water soluble penicillins, for instance Pen VK granules. The granulation of Pen VK is carried out using only water as binding solvent while no other additives (like binder materials) are required resulting in .beta.-lactam granules essentially free of organic solvent, viz. with no more organic solvents than the .beta.-lactams contain before the formation of granules.